Results of Questionnaire Survey of Current Immune Monitoring Practice of Transplant Clinicians and Clinical Pathologists in Korea: Basis for Establishment of Harmonized Immune Monitoring Guidelines

Eun-Suk Kang; Soo In Choi; Youn Hee Park; Geum Borae Park; Hye Ryon Jang

doi:10.4285/jkstn.2018.32.2.13

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Kang, Choi, Park, Park, and Jang: Results of Questionnaire Survey of Current Immune Monitoring Practice of Transplant Clinicians and Clinical Pathologists in Korea: Basis for Establishment of Harmonized Immune Monitoring Guidelines

Review Article

J Korean Soc Transplant 2018;32(2):13-25.

Published online: 19 January 2018

DOI: https://doi.org/10.4285/jkstn.2018.32.2.13

Results of Questionnaire Survey of Current Immune Monitoring Practice of Transplant Clinicians and Clinical Pathologists in Korea: Basis for Establishment of Harmonized Immune Monitoring Guidelines

Eun-Suk Kang, M.D.^1,, Soo In Choi, M.D.¹, Youn Hee Park, M.D.², Geum Borae Park, M.D.³, Hye Ryon Jang, M.D.⁴

¹Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

²Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

³Department of Laboratory Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea

⁴Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Corresponding author: Eun-Suk Kang Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea Tel: 82-2-3410-2703, Fax: 82-2-3410-2719 E-mail: eskang@skku.edu

Received 8 May 2018 Revised 4 June 2018 Accepted 5 June 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Detection of significant alloimmune response, which affects graft function and survival by effective immune monitoring, is critical for treatment decision making. However, there is no consensus regarding immune monitoring (IM) for kidney transplantation (flow KT) in Korea. The IM protocol may be affected by the level of immunological risk, the methods of desensitization and the availabilities of resources such as laboratory support and cost of tests. Questionnaire surveys designed to identify the current practices regarding immune monitoring of KT among transplant clinicians and clinical pathologists in Korea and eventually provide a basis for the establishment of harmonized immune monitoring guidelines in KT were administered as part of a Korean Society for Transplantation Sponsored Research Project. The survey results revealed significant variations in IM protocols and interpretation of tests affecting treatment decisions between institutes. Moreover, the results revealed a need to expand the histocompatibility tests into high resolution HLA typing in multiple loci and non-HLA antibody tests that facilitate the epitope analysis and eventually virtual crossmatching. The results of the questionnaire survey from clinical pathologists are addressing the urgent need for the standardization of interpretation and harmonization of results reporting in single antigen bead based HLA antibody identification. Finally, communication between clinicians and clinical pathologists to meet the clinical expectations regarding various immune monitoring tests is needed.

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Keywords: Kidney transplantation, Immunologic monitoring, Questionnaire survey

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Fig. 1.

Proportions of transplant clinicians responded in questionnaire surveys according to (A) specialties and (B) number of clinicians per single institute.

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Fig. 2.

The number of kidney transplantation performed per year in institutes where the transplant clinicians responded to questionnaire survey. Abbreviation: KT, kidney transplantation.

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Fig. 3.

Status of performing protocol biopsies after kidney transplantation. Responses of 32 clinicians from 25 institutes.

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Fig. 4.

Status of performing protocol biopsies depending on the level of immunological risk after kidney transplantation. The protocol biopsies are being performed in recipients with high immunological risk or regardless of immunological risk in different time points. Two clinicians responded that protocol biopsies are necessary on 1∼2 week and 12 week posttransplant. Responses of 32 clinicians from 25 institutes.

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Fig. 5.

Status of performing HLA antibody tests in (A) pre- and (B) post-kidney transplantation. Responses of 32 clinicians from 25 institutes. Abbreviation: SA ID, single antigen identification.

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Fig. 6.

Status of performing HLA antibody tests depending on the level of immunological risk after kidney transplantation. (A) HLA antibody screening test, (B) HLA antibody phenotyping test, and (C) HLA antibody single antigen identification test. Abbreviation: HLA, human leukocyte antigen.

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Fig. 7.

Suggested time points of HLA antibody monitoring test in patients waiting for kidney transplantation. Abbreviation: HLA, human leukocyte antigen.

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Fig. 8.

Indications of HLA antibody tests after kidney transplantation. Abbreviations: HLA, human leukocyte antigen; AMR, antibody mediated rejection.

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Fig. 9.

The threshold of %PRA to define high immunological risk in patients responded from 26 clinicians of 20 institutes. Abbreviation: PRA, percent reactive antibodies.

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Fig. 10.

Clinicians opinions about the need of further tests on histocompatibility. Abbreviation: HLA, human leukocyte antigen.

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Fig. 11.

Clinicians opinions about the need of further immune monitoring tests. Abbreviations: IGRA, interferon gamma releasing assay; CMV, cytomegalovirus; eGFR, estimated glomerular filtration rate.

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Fig. 12.

Clinicians opinions in areas which needs to be improved. Abbreviations: HLA, human leukocyte antigen; IM, immune monitoring.

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Fig. 13.

The principles of methods for HLA typing for kidney transplantation in responded laboratories according to the number of kidney transplantation performed per year in institutes. The data of three institutes referring HLA typing to outside labs are not included (∗) and the data of one institute of each performing HLA typing using two different methods are included (∗∗). Abbreviations: SSP, sequence-specific polymerase chain reaction; rSSOP, reverse sequence-specific oligonucleotide probe hybridization.

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Fig. 14.

HLA loci tested for kidney transplantation in responding laboratories. Abbreviation: HLA, human leukocyte antigen.

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Fig. 15.

The status of performing HLA antibody tests in responded laboratories according to the number of kidney transplantation performed per year in institutes. (A) Screening test, (B) Phenotyping, (C) Single antigen bead identification. Abbreviation: HLA, human leukocyte antigen.

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Fig. 16.

Clinical pathologist opinions on current shortcomings in laboratory practices.

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Table 1.

Clinicians opinions about the impact of immune monitoring tests on deciding treatment strategies regardless of current practices

Immune monitoring tests	Total	Effect	No effect	Not performing	No answer
HLA type matching	32	19 (59)	12 (38)	0 (0)	1 (3)
DSA(−) but high PRA	32	26 (81)	5 (16)	0 (0)	1 (3)
DSA (+)	32	31 (97)	0 (0)	0 (0)	1 (3)
DQ DSA alone	27	18 (67)	9 (33)	0 (0)	0 (0)
C or DP DSA alone	27	7 (26)	19 (70)	1 (3)	0 (0)
Complement binding antibody (+)	32	18 (56)	11 (34)	2 (6)	1 (3)
CDC crossmatching, T cell (+)	32	31 (97)	0 (0)	0 (0)	1 (3)
CDC crossmatching, B cell (+)	32	29 (91)	2 (6)	0 (0)	1 (3)
FCM crossmatching, T cell (+)	32	30 (94)	0 (0)	1 (3)	1 (3)
FCM crossmatching, B cell (+)	32	27 (84)	0 (0)	2 (6)	1 (3)
Biopsy finding	32	31 (97)	0 (0)	0 (0)	1 (3)
MIC antibody (+)	32	5 (16)	24 (75)	2 (6)	1 (3)
Lymphocyte subset analysis	32	4 (13)	27 (84)	0 (0)	1 (3)

Abbreviations: DSA, donor specific antibody; PRA, percent reactive antibody; CDC, complement dependent cytotoxicity; FCM, flow cytometry; MIC, MHC class I chain-related protein.

Table 2.

The threshold of DSA MFI in each locus to define high immunological risk in patients responded from 32 clinicians of 25 institutes

Threshold of DSA MFI	AB (n=26)	DR (n=26)	DQ (n=22)
1,000	6	7	6
2,000∼3,000	8	7	7
4,000	1	1	1
5,000	9	9	7
10,000	2	2	1
		c

Abbreviations: DSA, donor specific antibody; MFI, mean fluorescence intensity.

Table 3.

The format and content of single antigen bead based HLA antibody identification result reporting in different HLA laboratories (n=18)

Contents of SAB identification	No. of laboratories (%)
Resolution
Serological equivalent	7 (39)
Generic/allelic type	6 (33)
Both	5 (28)
Reporting of antibodies
Anti-DQB1	18 (100)
Anti-DPB1	11 (61)
Anti-DQA1 or -DPA1	9 (50)
Reporting of MFI values
MFI interval	7 (39)
Each MFI	9 (50)
MFI max	1 (6)
Not reporting	1 (6)
Reporting of % PRA
% cPRA	13 (72)
% cPRA including DQ antibodies	11 (61)
Each Class I and II	8 (44)
Combined Class I and II	2 (11)
Both	2 (11)

Abbreviations: SAB, single antigen bead; MFI, mean fluorescence intensity; % cPRA, % calculated percent reactive antibodies.

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